82 articles - From Friday Jul 15 2022 to Friday Jul 22 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| Haematologica |
Thrombosis in multiple myeloma: risk stratification, antithrombotic prophylaxis, and management of acute events. A consensus-based position paper from an ad hoc expert panel. e., thrombotic risk factors and risk stratification, primary thromboprophylaxis, management of acute thrombotic events, and secondary thromboprophylaxis. The issued recommendations may assist hematologists in minimizing the risk of thrombosis and guarantee adherence to treatment in patients with MM candidates to active treatment. |
meta-analyses and systematic reviews
RCT, clinical trials, retrospective studies, etc…
| Ann Oncol |
Circulating L-Arginine predicts the survival of cancer patients treated with immune checkpoint inhibitors. We demonstrate that baseline ARG levels predict ICI response. Plasma ARG quantification may therefore represent an attractive biomarker to tailor novel therapeutic regimens targeting the ARG pathway in combination with ICIs. |
Toripalimab (anti-PD-1) versus High-Dose Interferon-a2b as Adjuvant Therapy in Resected Mucosal Melanoma: A Phase II Randomized Trial. Toripalimab showed a similar RFS and a more favorable safety profile than HDI, both better than historical data, suggesting that toripalimab might be the better treatment option. However, additional translational studies and better treatment regimens are still warranted to improve the clinical outcome of MM. |
| Blood |
Developing a Classification of Hematologic Neoplasms in the Era of Precision Medicine. A collaborative clinico-pathologic review process will provide a mechanism to update pathologic and genomic criteria within a clinical context. An interactive web-based portal would make the classification more immediately available to the scientific community, while providing accessory features enabling practical application of diagnostic, prognostic, and predictive information. |
Epigenetic regulator genes direct lineage switching in MLL/AF4 leukaemia. The relapsed myeloid phenotype is recurrently associated with the altered expression, splicing or mutation of chromatin modifiers, including CHD4 coding for the ATPase/helicase of the nucleosome remodelling and deacetylation complex, NuRD. Perturbation of CHD4 alone or in combination with other mutated epigenetic modifiers induces myeloid gene expression in MLL/AF4-positive cell models indicating that lineage switching in MLL/AF4 leukaemia is driven and maintained by disrupted epigenetic regulation. |
Erythroblastic islands foster granulopoiesis in parallel to terminal erythropoiesis. Finally, by molecular profiling, we reveal the heterogeneity of EBI macrophages by Cellular Indexing of Transcriptome and Epitopes (CITE)-sequencing of mouse bone marrow EBIs at baseline and after Epo-stimulation in vivo and provide a searchable, online viewer of this data characterizing the macrophage subsets serving as hematopoietic niches. Taken together, our findings demonstrate that EBIs serve a dual role as niches for terminal erythropoiesis and granulopoiesis and the central macrophages adapt to optimize production of red blood cells or neutrophils. |
Moderate-intensity aerobic exercise versus desmopressin in adolescent males with mild hemophilia A: a randomized trial. More than 60% of participants randomized to receive both exercise and desmopressin achieved normal (>50%) FVIII:C, 75- and 135-minutes into the study protocol. NCT03379974; NCT03136003. |
Patient-reported outcomes in ZUMA-7, a phase 3 study of axicabtagene ciloleucel in second-line large B-cell lymphoma. Axi-cel showed clinically meaningful improvements in QoL over SOC. Superior clinical outcomes and favorable patient experience with axi-cel should help inform treatment choices in second-line R/R LBCL. |
Targeting MDM2 enhances anti-leukemia immunity after allogeneic transplantation via MHC-II and TRAIL-R1/2 upregulation. Patient-derived AML-cells exhibited increased TRAIL-R1/2 and MHC-II expression upon MDM2-inhibition. In summary, we identified a targetable vulnerability of AML cells to allogeneic T-cell-mediated cytotoxicity, through restoration of p53-dependent TRAIL-R1/2 and MHC-II-production via MDM2-inhibition. |
Venetoclax synergizes with Gilteritinib in FLT3 wildtype high-risk Acute Myeloid Leukemia by suppressing MCL-1. In summary, our results suggest that combined inhibition of FLT3/AXL potentiates venetoclax response in FLT3-wildtype AML by inducing MCL-1 degradation. Thus, the venetoclax-gilteritinib combination merits testing as potentially active regimen in high-risk AML patients with FLT3 wildtype. |
| Blood Adv |
Causes of Death in Low Grade B-Cell Lymphomas in the Rituximab Era: A Prospective Cohort Study. In conclusions, the most common COD in LGBCLs in the first decade after diagnosis was for causes other than lymphoma. Progression or retreatment within the first 2 years of diagnosis was a strong predictor for risk of lymphoma-related death. |
Defective RAB31-mediated megakaryocytic early endosomal trafficking of VWF, EGFR, and M6PR in RUNX1 deficiency. There was loss of plasma membrane VWF in RUNX1- and RAB31- deficient megakaryocytic HEL cells, and RHD-iMKs These studies provide evidence that RAB31 is downregulated in RUNX1 haplodeficiency and regulates megakaryocytic vesicle trafficking of 3 major proteins with diverse biological roles. Early endosome defect and impaired vesicle trafficking is a potential mechanism for the |
Differences in wild type- and R338L-tenase complex formation are at the root of R338L-factor IX assay discrepancies. Supplementing FX into CSA had the effect of dampening FIX-WT activity relative to R338L-FIX activity, suggesting that FX impairs WT tenase formation to a greater extent than R338L-FIX tenase. Our data describe the scale of R338L-FIX assay discrepancies and provide insights into the causative mechanisms that will help establish best practices for the measurement of R338L-FIX activity in patients after gene therapy. |
Disparities in trial enrollment and outcomes of Hispanic adolescent and young adult acute lymphoblastic leukemia. In summary, Hispanic patients treated on CALGB 10403 did as well as NHWs and better than population estimates. Geographical misalignment between trial sites and disease epidemiology may partially explain the lower-than-expected enrollment of Hispanic AYA ALL patients. |
Intraosseous delivery of platelet-targeted FVIII lentiviral vector in humanized NBSGW mice. Most importantly, IO delivery of G-F8-LV to humanized NBSGW mice produced persistent FVIII expression in human platelets after gene therapy, and the megakaryocytes differentiated from human CD34+ HSPCs isolated from LV-treated humanized mice showed up to 10.2% FVIII expression, indicating efficient transduction of self-regenerating human HSPCs. Collectively, these results indicate the long-term safety and efficacy of IO-LV gene therapy strategy for hemophilia A in a humanized model, adding further evidence to the feasibility of translating this method for clinical applications. |
Membrane curvature and PS localize coagulation proteins to filopodia and retraction fibers of endothelial cells. Our results indicate that stressed or stimulated endothelial cells support prothrombinase activity localized to convex topological features at cell margins. These findings may relate to perivascular fibrin deposition in sepsis and inflammation. |
Neighborhood disadvantage, health status, and healthcare utilization after blood or marrow transplant: BMTSS report. In BMT survivors, access to healthcare and health status are associated with area disadvantage. These findings may inform strategies to address long-term care coordination and retention for vulnerable survivors. |
NK cell CD56bright and CD56dim subset cytokine loss and exhaustion is associated with impaired survival in myeloma. These results suggest that NK cell exhaustion is already present by the time of myeloma diagnosis and likely contributes to the loss of immunological control of malignant plasma cells. Restoring NK cell function via immune directed therapies offers a route to restoring immunological control in multiple myeloma. |
Quality of Life, Psychological Distress, and Prognostic Perceptions in Caregivers of Patients with Multiple Myeloma. The majority of caregivers of patients with MM report that knowing the patient's prognosis is extremely important and report that the oncologist told them that the patient was incurable. Nevertheless, a significant portion of caregivers believe that the patient's MM is curable. |
The safety and efficacy of N8-GP (turoctocog alfa pegol) in previously untreated pediatric patients with hemophilia A. The inhibitor incidence was 29.9%. All patients with temporarily decreased IR continuing on N8-GP dosing returned within the expected range and had no evident lack of efficacy. |
Total marrow and lymphoid irradiation as conditioning in haploidentical transplant with posttransplant cyclophosphamide. For patients treated with 2000 cGy, with a median follow-up duration of 12.3 months, 1-year relapse/progression, progression-free survival, and overall survival rates were 17%, 74%, and 83%, respectively. In conclusion, HaploHCT-TMLI with PTCy was safe and feasible in our high-risk patient population with promising outcomes. |
| Blood Cancer J |
BRD9 degraders as chemosensitizers in acute leukemia and multiple myeloma. Degradation of BRD9 potentiated the effects of several chemotherapeutic agents and targeted therapies against AML, ALL, and MM. Our findings support further development of therapeutic targeting of BRD9, alone or combined with other agents, as a novel strategy for acute leukemias and MM. |
Long-term follow-up of cladribine treatment in hairy cell leukemia: 30-year experience in a multicentric Italian study. Forty-nine patients died (9.5%), following an infection in 14 cases (2.7%), natural causes in 14 (2.7%), cardiovascular events in 13 (2.5%), a second neoplasm in 6 (1.2%), and progression of HCL in 2 cases (0.4%). Following treatment of HCL with 2CDA, 80% of patients are estimated to be alive 15 years after diagnosis. |
| Haematologica |
Hypercortisolemic Cushing's patients possess a distinct class of hematopoietic progenitor cells leading to erythrocytosis. Collectively, these results indicate that chronic exposure to excess glucocorticoids in vivo leads to erythrocytosis by generating erythroid progenitor cells with a constitutively active GR. Although remission rescues the erythrocytosis and the phenotype of the circulating CD34+ cells, a memory of other prior changes is maintained in remission. |
Improved outcomes with 7+3 induction chemotherapy for acute myeloid leukemia over the past four decades: analysis of SWOG trial data. The relative benefit associated with CR1 and the relative detriment associated with relapse have decreased over this period; while achieving CR1 and relapse from CR1 still have strong prognostic associations with outcomes, the magnitude of the association has decreased over time. Possible explanations for these patterns include higher CR rates with salvage therapies after relapse, more frequent use of hematopoietic cell transplant, and better supportive care. |
PDL1 shapes the classical Hodgkin lymphoma microenvironment without inducing T cell exhaustion. Instead, we identified a strong association between PDL1 expression and CHL MHC-II expression, TH recruitment, and enrichment of Th1 regulatory cells. These data suggest that a dominant effect of PDL1 expression in CHL may be T helper engagement and promotion of regulatory microenvironment rather than maintenance of exhaustion. |
RHOA regulated IGFBP2 promotes invasion and drives progression of BCR-ABL1 chronic myeloid leukemia. This elevated IGFBP2 expression is confirmed in primary CML samples. Thus, we demonstrate one mechanism whereby RHOA-SRF-IGFBP2 signaling axis contributes to development of leukemia in cells expressing the p210 BCRABL1 fusion kinase. |
Time spent at home among older adults with acute myeloid leukemia receiving azacitidine- or venetoclax-based regimens. PDH did not differ between therapy groups (adjusted mean, AZA+VEN: 0.68; AZA monotherapy: 0.66; p=0.64) or between disease risk categories (p=0.34). Compared to AZA monotherapy, patients receiving AZA+VEN had longer clinic visits (median minutes: 127.9 vs 112.9, p. |
| J Hematol Oncol |
Allosteric activation of the metabolic enzyme GPD1 inhibits bladder cancer growth via the lysoPC-PAFR-TRPV2 axis. This study suggests that GPD1 may act as a novel tumor suppressor in bladder cancer. Pharmacological activation of GPD1 is a potential therapeutic approach for bladder cancer. |
hUC-EVs-ATO reduce the severity of acute GVHD by resetting inflammatory macrophages toward the M2 phenotype. hUC-EVs-ATO enhanced the alleviation of aGVHD severity in mice compared with ATO and hUC-EVs without weakening GVL activity. hUC-EVs-ATO promoted M1 to M2 polarization via the mTOR-autophagy pathway. hUC-EVs-ATO could be a potential therapeutic approach in aGVHD after allo-HSCT. |
| Lancet Haematol |
| Leukemia |
APR-246 triggers ferritinophagy and ferroptosis of diffuse large B-cell lymphoma cells with distinct TP53 mutations. TP53 mutations on exons 5, 6 and 7 are predictors of progression and survival. Targeting mutant p53 by APR-246 is a promising therapeutic approach for DLBCL patients. |
Reproducible measurable residual disease detection by multiparametric flow cytometry in acute myeloid leukemia. MRD defined by this strategy provides relevant prognostic information and establishes aberrancies outside of cell populations with markers of immaturity as an independent risk feature. Our results imply that this strategy may provide the base for multicentric immunophenotypic MRD assessment. |
| Thromb Haemost |
The Platelet Lipidome Is Altered in Patients with COVID-19 and Correlates with Platelet Reactivity. Taken together, this investigation provides the first exploration of the profound impact of infection on the human platelet lipidome, and reveals associations between the lipid composition of platelets and their reactivity. These results warrant further lipidomic research in other infections and disease states involving platelet pathophysiology. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Blood |
| J Hematol Oncol |
Emerging strategies to overcome resistance to third-generation EGFR inhibitors. In view of resistance to third-generation inhibitors, understanding the intricate mechanisms of resistance will offer insight for the development of more advanced targeted therapies. In this review, we discuss the molecular mechanisms of resistance to third-generation EGFR inhibitors and review recent strategies for overcoming resistance, new challenges, and future development directions. |
Exploring immunotherapy in colorectal cancer. Clinical trials examining the effect of immune checkpoints are actively carried out, in order to produce long-lasting effects for mCRC patients. This review summarizes the treatment strategies for mCRC patients, discusses the mechanism and application of ICB in mCRC treatment, outlines the potential markers of the ICB efficacy, lists the key results of the clinical trials, and collects the recent basic research results, in order to provide a theoretical basis and practical direction for immunotherapy strategies. |
Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management. Here, we review the most recent literature to summarize the molecular mechanisms underlying mitochondrial stress adaptation and their intricate connection with cancer drug resistance. In addition, an overview of the emerging strategies to target mitochondria for effectively overcoming chemoresistance is highlighted, with an emphasis on drug repositioning and mitochondrial drug delivery approaches, which may accelerate the application of mitochondria-targeting compounds for cancer therapy. |
Targeting p53-MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials. This review focused on the discovery, structural modification, preclinical and clinical research of the above compounds from the perspective of medicinal chemistry. Based on this, the possible defects in MDM2 inhibitors in clinical development were analyzed to suggest that the multitarget strategy or targeted degradation strategy based on MDM2 has the potential to reduce the dose-dependent hematological toxicity of MDM2 inhibitors and improve their anti-tumor activity, providing certain guidance for the development of agents targeting the p53-MDM2 interaction. |
The mitochondrial unfolded protein response (UPRmt): shielding against toxicity to mitochondria in cancer. UPR mt is conserved and activated in cancer in response to mitochondrial stress to maintain mitochondrial integrity and support tumor growth. In this review, we discuss how mitochondria become dysfunctional in cancer and highlight the tumor-promoting functions of key components of the UPR mt . |
Letters to the editors and authors’ replies
| Am J Hematol |
| Blood |
| J Hematol Oncol |
Predictive factors and outcomes for ibrutinib in relapsed/refractory marginal zone lymphoma: a multicenter cohort study. Only primary refractory disease to first-line therapy predicted a higher probability of PP to ibrutinib (RR |
all remaining publications eg case reports, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| Lancet Haematol |
| Leukemia |